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Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer. [ABSTRACT FROM AUTHOR]

AbstractAimMethodsResultsConclusions\nSTRENGTHS AND LIMITATIONS OF THIS STUDYLambl’s excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl’s excrescences are associated with migraine.Retrospective review of 182 inpatients with Lambl’s excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl’s excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits.A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl’s excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl’s excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications.This study supports the hypothesis that microemboli from isolated Lambl’s excrescences could cause migraine-like headache. And intervention for Lambl’s excrescences may be crucial for preventing headache recurrence.This study supports the hypothesis that microemboli from isolated Lambl’s excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations.This study supports the hypothesis that microemboli from isolated Lambl’s excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations. [ABSTRACT FROM AUTHOR]

Single crystal superalloys are widely used in the manufacturing of turbine blades for aero-engines due to their superior performance at high temperatures. The directional solidification process is a key technology for producing single crystal turbine blades with excellent properties. In the directional solidification process, withdrawal rate is one of the critical parameters for microstructure formation and will ultimately determine the blade's properties. In this paper, the as-cast microstructures in the typical sections of a DD9 single crystal (SX) superalloy turbine blade were investigated with 3 mm/min and 5 mm/min withdrawal rates during the directional solidification process. With increased withdrawal rate, the dendrite morphologies tended to become more refined, and the secondary dendritic arms tended to be highly developed. The dendrite in the blade aerofoil section was more refined than that in the tenon section, given the same withdrawal rate. Additionally, with increasing withdrawal rates, the size and dispersity of the γ′ precipitates in the inter-dendritic (ID) regions and dendritic core (DC) tended to decrease; furthermore, the size distributions of the γ′ precipitates followed a normal distribution law. Compared with the ID regions, an almost 62% reduction in the average γ′ sizes was measured in the DC. Meanwhile, given the same withdrawal rate, at the blade's leading edge closest to the heater, the γ′ sizes in the aerofoil section (AS) were more refined than those in the tenon section (TS). As compared with the decreasing cross-sectional areas, the increased withdrawal rates clearly brought down the γ′ sizes. The sizes of the γ–γ′ eutectics decreased with increasing withdrawal rates, with the γ–γ′ eutectics showing both lamellar and rosette shapes. [ABSTRACT FROM AUTHOR]

[Display omitted] Industry for producing the vital chemical hydrogen peroxide (H 2 O 2) requires drastically reductions in energy consumption and environmental pollution. Solar chemical conversion from O 2 to H 2 O 2 is considered to be the most promising alternative method, nevertheless, weak energy coupling between photo-charges and adsorbed species limits the yield of H 2 O 2. Herein, we demonstrate that oxygen vacancy-rich BiVO 4 can efficiently generate H 2 O 2 in pure water under visible light irradiation without any heterojunctions or precious-metal cocatalysts. Oxygen vacancies, as typical coordinatively unsaturated sites, enable efficient O 2 adsorption and enrichment, and then thriving chemisorption can spatially facilitate photoexcited electrons transfer to oxygen species. Compared to pristine BiVO 4 , defective BiVO 4 enhanced O 2 adsorption and interfacial electron transfer rate to O 2 by 19 and 23 times, respectively, resulting in a more than 32-fold increase in H 2 O 2 production. This research offers a new perspective for bridging solar and chemical energy by assuring species chemisorption. [ABSTRACT FROM AUTHOR]

Introduction: To explore the clinical efficacy of the enhanced recovery after surgery (ERAS) program in terms of blood management for primary hip arthroplasty patients. Method: Ninety cases of total hip arthroplasty in our hospital from October 2020 to January 2022 were selected as the research objects, 45 cases as the control group, and 45 cases as the ERAS group. The control group was given routine care after operation, while the ERAS group was given ERAS management. The leucocytes, haemoglobin, platelets, albumin, D-dimer, C-reactive protein (CRP), total length of stay (LOS), and estimated blood loss after operation were compared between the two groups. Results: The results showed that the Hb, TPO, and Alb of the ERAS group before operation, one day and three days after operation were significantly higher than those of the control group (P < 0.05). The WBC, CRP, and D-dimer in ERAS group were significantly lower than those in the control group (P < 0.05). The LOS in ERAS group was significantly less than that in control group (P < 0.05). Discussion: ERAS scheme can reduce the loss of blood and nutrients from surgery in patients. WBC, CRP, and D-dimer in ERAS group were significantly lower than those in the control group. Humane care from ERAS programs can relieve patients' anxiety to some extent. Conclusion: ERAS management contributes to the recovery of hip function in patients undergoing THA, reduces blood loss during peri-operative period, and reduces the effect of operation on blood system. [ABSTRACT FROM AUTHOR]

Purpose: Belowground carbon (C) allocation for nitrogen (N) acquisition plays a crucial role in determining primary productivity and plant competitiveness in legume-grass mixtures, but beyond modeling and qualitative assessments, this remains poorly understood, especially with regard to drought stress and interspecific interactions. Methods: We grew a legume (Trifolium repens) and a grass (Lolium perenne) in monocultures and as a 50:50 mixture (with same plant density), at 70% and 50% soil water holding capacity representing non-drought and drought conditions, for 104 days in a growth chamber experiment. By using continuous 13CO2 labelling and 15N pulse soil-labelling, we analyzed how drought and interspecific interaction affected belowground C allocation (including root biomass, root respiration and rhizodeposition) and N acquisition through soil N uptake and biological N fixation. Results: Drought increased belowground C allocation per unit of N acquisition in the legume, but not in the grass. Drought significantly reduced biological N fixation in the legume, so that the legume allocated relatively more C to take up soil N. Interspecific competition increased belowground C allocation per unit of N acquisition, which could be attributed to a reduction in biological N fixation by the legume and an increased abundance of the grass. Conclusions: We highlight that drought and interspecific competition for N strongly alter C allocation towards biological N fixation and soil N uptake. Our measurements provide important process-based information to improve modeling drought effects on productivity and composition in legume-grass mixtures. [ABSTRACT FROM AUTHOR]

Natural fractures are important reservoirs and migration channels for tight oil and gas systems, and the various geological geneses of fractures are key factors that determine whether tight oil and gas can be produced. Therefore, research on identifying and characterizing the origins of fractures has become critical, especially the challenge of using conventional logging data to identify and characterize fractures with various geological geneses, and an efficient characterization method is urgently needed. First, core observation, thin section analysis, core sample test analysis, numerical simulation, core calibration of borehole-imaging logs, and borehole-imaging log calibration of conventional logs are performed to identify the sensitive logging curves and log response characteristics of fractures with different geological geneses. Second, the response characteristics of and differences in the log and rock physical properties of tight sandstone with fractures, without fractures and with fractures having different origins are analyzed, and the logging eigenvalue and rock physical eigenvalue models, which are comprehensive identification methods, are established, as are criteria for determining the different causes of fractures in tight sandstones. Finally, the two models are applied to identify and characterize the geological geneses of fractures in tight sandstone reservoirs in Sichuan. The effect of using the logging eigenvalue and the rock physical eigenvalue models to identify fractures is consistent with that using an imaging log. [ABSTRACT FROM AUTHOR]

We study fracture activation and induced seismicity during the long-term heat production of fractured geothermal reservoirs. The fracture system is modeled by the discrete fracture network approach that realistically represents the distribution and behavior of natural fractures in the system. Using a novel fully coupled thermal-hydro-mechanical model, we systematically investigate the interplay among in situ stresses, injection pressure and temperature on the spatio-temporal evolution of heat production-induced seismicity. Our results show that in situ stress state exerts a fundamental background control on the seismicity occurrence, while injection-induced fluid pressurization and thermal perturbation act as two competing triggering factors. Induced seismic events occur mainly in the near field of the injection well and along the main streamlines of fluid flow through the reservoir. Under a low differential stress condition, fracture activation is dominated by late-stage thermal drawdown, such that the injection temperature controls the timing, magnitude and number of seismic events. However, under a high differential stress condition, the effect of early-stage pressurization dominates with critically stressed fractures activated once or twice. The fracture activation is sensitive to the variation of pressure gradient, whilst the injection temperature attempts to influence the magnitude but in general not the timing and number of thermal drawdown-induced secondary seismic events. Furthermore, these anthropogenic parameters (i.e. injection pressure and temperature) strongly affect the long-term thermal energy output of the reservoir. Our research findings have important implications for the mitigation of seismic hazards by optimizing production strategy design during heat extraction from deep geothermal reservoirs. Highlights: The interplay among in situ stresses, injection pressure and temperature on long-term heat production-induced seismicity is investigated. The seismicity triggering mechanism by simultaneous, transient propagations of hydrodynamic and thermal fronts is quantified. The spatial pattern of recurrent seismicity driven by thermal front migration in a critically stressed fracture system is analyzed. [ABSTRACT FROM AUTHOR]

Objective. Biomarkers for pancreatic cancer (PCa) prognosis provide evidence for improving the survival outcome of this disease. This study aimed to identify a prognostic risk model based on gene expression profiling of microarray bioinformatics analysis. Methods. Prognostic immune genes in the TCGA-PAAD cohort were identified using the univariate Cox regression and Kaplan–Meier survival analysis. Multivariate Cox regression (stepAIC) was used to identify prognostic genes from the top 20 hub genes in the protein-protein interaction (PPI) network. A prognostic risk model was established and its performance in predicting the overall survival in PCa was validated in GSE62452. Gene mutations and infiltration immune cells in PCa tumors were analyzed using online databases. Results. Univariate Cox regression and Kaplan–Meier survival analyses identified 128 prognostic genes. Multivariate Cox regression (stepAIC) identified five prognostic genes (PLCG1, MET, TNFSF10, CXCL9, and TLR3) out of the 20 hub genes in the PPI network. A prognostic risk model was established using the signature of five genes. This model had moderate to high accuracies (AUC > 0.700) in predicting 3-year and 5-year overall survival in TCGA and GSE62452 cohorts. The Kaplan–Meier survival analysis showed that high-risk scores were correlated with poor survival outcomes in PCa (p < 0.05). Also, mutations in the five genes were related to poor survival. The five genes were related to multiple immune cells. Conclusions. The prognostic risk model was significantly correlated with the survival in PCa patients. This model modulated PCa tumor progression and prognosis by regulating immune cell infiltration. [ABSTRACT FROM AUTHOR]

Students and junior researchers are important stakeholders in scholarly publishing, but there is relatively little research into their reading needs and barriers. This study hoped to understand the similarities and differences between junior researchers and students, between this group and more senior researchers and between different disciplines. The research comprised two parts: initial interviews to ascertain the main barrier and needs items, followed by a large‐scale online survey. The survey received 673 responses from Chinese students and junior researchers. The survey revealed that poor presentation leading to poor understanding was a common barrier, but there were disciplinary differences, with humanities scholars having fewer barriers than other disciplines. Postgraduates reported more barriers than undergraduates, and also scored information needs more highly. The results identify needed improvements in the presentation of articles and explanation of terminology in order to better engage with students and junior researchers. [ABSTRACT FROM AUTHOR]

This paper proposes an approach for finite element (FE) model updating and response prediction of frame structures based on optimal sensor placement (OSP), which integrates sensor placement optimization, mode expansion, and model updating techniques. Firstly, sensor optimization layout and modal testing analysis are conducted on a bolted laboratory frame structure. The covariance-driven stochastic subspace identification (SSI-COV) method identifies the real-world structure’s natural frequencies, modal damping, and mode shapes. Secondly, the complete mode shapes are expanded using the measured incomplete modal data from the limited number of sensors. Thirdly, a multi-objective function based on frequency and mode shapes is established to adjust the parameters of the FE model. This ensures that the updated model accurately represents the dynamic properties of the actual structure within a specific frequency range. Finally, the Rayleigh damping of the frame structure is estimated, and the damping matrix is assembled to enhance the accuracy of dynamic response prediction in the updated model. By comparing the response prediction results of the updated FE model with and without considering the updated damping effects to the measurement data of the real-world structure, it is demonstrated that the proposed method considering updated damping effects can more effectively predict the structural response. [ABSTRACT FROM AUTHOR]

Piers and bearings influence each other in earthquakes, and the failure of any component will affect the whole function of bridges. Thus, it is critical to consider the correlations between multiple components in the seismic vulnerability analysis of the overall bridge system. In this paper, a method of overall seismic vulnerability analysis with nested copula model was proposed to model the correlations between multiple components. The components were combined according to their types to construct the hierarchical structure of the system. The correlation of components was modeled with copula functions, and the nested copula model of the system was eventually developed. Maximum likelihood estimation and goodness-of-fit test were used to select and optimize the copula functions. The overall seismic vulnerability of the multispan bridge system was established using the nested copula model. A four-span continuous rigid frame bridge was used to illustrate the application of the proposed method. The results show that the nested copula model accurately simulated the correlations between multiple components, which would eliminate the overestimation or underestimation by the first-order boundary method. [ABSTRACT FROM AUTHOR]

Scientific papers are essential manifestations of evolving scientific knowledge, and arguments are an important avenue to communicate research results. This study aims to understand how the argumentation process is represented in scientific papers, which is important for knowledge representation, discovery, and retrieval. First, based on fundamental argument theory and scientific discourse ontologies, a coding schema, including 17 categories was constructed. Thereafter, annotation experiments were conducted with 40 scientific articles randomly selected from two different research areas (library and information science and biomedical sciences). Statistical analysis and the sequential pattern mining method were then employed; the ratio of different argumentation units and evidence types were calculated, the argumentation semantics of figures and tables analyzed, and the argumentation structures extracted. A correlation analysis between argumentation and rhetorical structures was also performed to further reveal how argumentation was represented within scientific discourses. The results indicated a difference in the proportion of the argumentation units in the two types of scientific papers, as well as a similar linear construction with differences in the specific argument structures of each knowledge domain and a clear correlation between argumentation and rhetorical structure. [ABSTRACT FROM AUTHOR]

A hexagonal honeycomb magnetic tunneling junction array with 72 nm pitch and 30 nm MgO critical dimension was successfully fabricated on a 1× nm dynamic random access memory platform by using a mature dynamic random access memory patterning solution and ion beam etch. To our knowledge, both pitch size and critical dimension size are the world's smallest ones for industrial magnetic tunneling junction arrays. To obtain such a high density and small sized magnetic tunneling junction array, a cross self-aligned double patterning technique, a triple layer hard mask scheme, and an optimized ion beam etch condition were adopted. During the optimization of the ion beam etch process, the dependence of a magnetic tunneling junction pillar profile on ion beam etch parameters for a high density hexagonal magnetic tunneling junction array has also been systematically studied. The depth of oxide recess and the magnetic tunneling junction sidewall angle increased with the ion beam etch amount, while magnetic tunneling junction critical dimension and hard mask remainder thickness decreased with increasing ion beam etch amount. [ABSTRACT FROM AUTHOR]

Data repositories are an essential component of data infrastructure. This article explores their functionalities with accompanying examples with a focus on open, quantitative data sets. Based on researcher needs, the principle of data friendliness is presented, which involves data context (data characteristics), research context (individual circumstances and research settings) and the context of reuse paths (conditions allowing access to, understanding of and use of data). An examination of data context suggests that metadata and data enrichment are required to provide successful data context. Enrichment is also required for orientation of the research context to provide greater insights across data sets. Finally the article considers the reuse paths, and the say that data paths intersect human interaction and how these are being addressed by different repositories. The review concludes that data repositories need to focus on how to present data that is fully interoperable and allows for reuse as well as access. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multicomponent oil flow regime in authentic shale nanopores was determined. • Flow regime transition led to nonlinear flux increase with pressure gradient. • Oil desorption and redistribution shifted flow regime from parabolic to piston-like. • Widening nanopore altered flow regime enhancing flow in quartz nanopores. • Increasing temperature facilitated oil desorption and expansion enhancing flow. Understanding the shale oil flow mechanism in nanopores is crucial for optimizing development strategies and enhancing recovery in shale oil reservoirs. Despite the widespread use of molecular dynamics simulations in studying shale oil flow, oversimplified shale oil and shale nanopore models compromise result reliability, and a definitive shale oil flow regime has yet to be established. This study, employing validated molecular models, investigated 26-component oil flow in authentic shale kerogen and quartz nanopores. For the first time, we elucidated the nonlinear flux increase due to flow regime transition with pressure gradient. At low pressure gradients, shale oil flux gradually increased with a parabolic velocity profile. With the increasing pressure gradient, the velocity profile shifted from parabolic to piston-like, especially in quartz nanopores, indicating a positive slip velocity. Consequently, the shale oil flux increased significantly. At high pressure gradients, the growth of shale oil flux decelerated while maintaining a piston-like velocity profile. Through analysis of density distribution and oil-wall interactions, we revealed that oil desorption and redistribution triggered the flow regime transition. The flow regime transition occurred with the widening of quartz nanopores. Increased nanopore width and temperature notably enhanced shale oil flow. This study underscored the importance of accounting for shale oil's multicomponent properties and roughness and composition of shale nanopores. It determined shale oil flow regimes under various conditions, advancing our comprehension of shale oil flow mechanisms in realistic settings and furnishing a theoretical foundation for enhancing shale oil recovery. [ABSTRACT FROM AUTHOR]

Well isolated 72 nm pitch hexagonal honeycomb magnetic tunneling junction (MTJ) array with about 45 nm MgO CD was successfully fabricated on a DRAM platform by using mature DRAM array patterning solution with self-aligned double patterning technology and proposed triple hard mask scheme. The 72 nm pitch MTJ array had an equivalent cell size as small as $0.0044~\mu \text{m}$ 2, the world’s smallest pitch size and cell size for industrial MTJ array to our knowledge. The hexagonal array geometry offered considerably merit for storage density enhancement and MTJ etch convenience. A reactive ion etch (RIE) and ion beam etch (IBE) combined MTJ etching solution was adopted to optimize pillar isolation and mitigate metallic re-deposition and etch damage. Perpendicular magnetic anisotropy was maintained in MTJ array; however, free layer coercivity was smaller than expected, indicating the existence of etch damage or fringe magnetic field interaction. Potential challenges for the chip integration of high-density hexagonal MTJ array are also discussed. [ABSTRACT FROM AUTHOR]

Data reuse has recently become significant in academia and is providing new impetus for academic research. This prompts two questions: What precisely is the data reuse process? What is the connection between each participating element? To address these issues, 42 studies were reviewed to identify the stages and primary data reuse elements. A meta‐synthesis was used to locate and analyze the studies, and inductive coding was used to organize the analytical process. We identified three stages of data reuse—initiation, exploration and collection, and repurposing—and explored how they interact and form iterative characteristics. The results illuminated the data reuse at each stage, including issues of data trust, data sources, scaffolds, and barriers. The results indicated that multisource data and human scaffolds promote reuse behavior effectively. Further, two data and information search patterns were extracted: reticular centripetal patterns and decentralized centripetal patterns. Three paths with elements cooperating through flexible functions and motivated by different action items were identified: data centers, human scaffolds, and publications. This study supports improvements for data infrastructure construction, data reuse, and data reuse research by providing a new perspective on the effect of information behavior and clarifying the stages and contextual relationships between various elements. [ABSTRACT FROM AUTHOR]

In this study, we report an efficient fabrication method for the membrane of a metal‐organic framework (MOF) (Kgm−OEt) which is one kind of kagomé‐type MOF with a two‐dimensional (2D) sheet structure having one‐dimensional (1D) channels suitable for separation of H2 from other larger gases. The Kgm−OEt seed layer was created on an Al2O3 substrate using layer‐by‐layer (LBL) growth, then a membrane was fabricated by secondary growth. The membrane on a 3‐aminopropyltriethoxysilane (APTEs)‐treated substrate obtained in this method was continuous and defect‐free with the crystal orientation suitable for gas transportation, while the membrane grown on an unmodified substrate was loosely packed with unfavorable crystal orientation. [ABSTRACT FROM AUTHOR]

Purpose: To meet the emerging demand for fine-grained annotation and semantic enrichment of cultural heritage images, this paper proposes a new approach that can transcend the boundary of information organization theory and Panofsky's iconography theory. Design/methodology/approach: After a systematic review of semantic data models for organizing cultural heritage images and a comparative analysis of the concept and characteristics of deep semantic annotation (DSA) and indexing, an integrated DSA framework for cultural heritage images as well as its principles and process was designed. Two experiments were conducted on two mural images from the Mogao Caves to evaluate the DSA framework's validity based on four criteria: depth, breadth, granularity and relation. Findings: Results showed the proposed DSA framework included not only image metadata but also represented the storyline contained in the images by integrating domain terminology, ontology, thesaurus, taxonomy and natural language description into a multilevel structure. Originality/value: DSA can reveal the aboutness, ofness and isness information contained within images, which can thus meet the demand for semantic enrichment and retrieval of cultural heritage images at a fine-grained level. This method can also help contribute to building a novel infrastructure for the increasing scholarship of digital humanities. [ABSTRACT FROM AUTHOR]

• A novel probability algorithm based on fuzzy information diffusion is proposed to track the global maximum power point. • This method is a probabilistic algorithm based on interval estimation. • Without the random searching process, this method can track the maximum power point quickly. Under stochastic partial shading conditions, the photovoltaic power system often produces a non-convex characteristic curve. It makes the maximum power point tracking a difficult task. In this paper, based on fuzzy information diffusion, a novel probability algorithm is proposed to track the global maximum power point (GMPP) under partial shading conditions. By uniform incomplete sampling and information diffusion, the proposed method can avoid the random searching process of intelligence algorithms, which will effectively improve the tracking speed and global search capability. From the perspective of probability estimation, the information diffusion function is used to fill the information gap caused by incomplete sampling data, thus transforming the discrete sampling points of PV system into a continuous distribution function. According to the fuzzy probability, one or more discrete intervals are selected to estimate the real value of GMPP. At last, the variable step-size P&O method is adopted to get a more accurate result in these selected intervals. In fact, the information diffusion is a global fuzzy probability estimation algorithm. It has a good global search characteristic. The comprehensive simulations and experiments have fully demonstrated the efficacy and applicability of the proposed method in this paper. [ABSTRACT FROM AUTHOR]

To describe materials deformation with viscoplastic characteristics, the Anand model is usually used. For a certain material, the classical method based on the saturation stress of material deformation is usually adopted to identify the parameters in its Anand model. However, for some materials, the saturation stress can not be obtained in the measurable strain range of general experiment equipment, and the classical method should be modified for this situation. Hence in this paper, a method used to identify the saturation stress of material from the insaturation state of deformation is proposed. For the proposed method, the identification of saturation stress is transferred to a problem of obtaining the solution of an objective function, which is derived from the stress-strain curves of insaturation state. By combining the proposed method, the classical Anand parameters identification method can be used in a wider range than before. [ABSTRACT FROM AUTHOR]

The interacting model describing the Rabi transition is essential in studying atom-photon interactions, where the kinetic energy term is often neglected for the convenience of analysis. We first study the approximation through the fidelity approach and verify its valid region in the parameter space of detuning and momentum. We find that as the radiation field's momentum and the absolute value of detuning decrease, the approximation becomes valid. We further discover that the omission of the kinetic energy term will overestimate the measuring accuracy of the Rabi frequency in some parameter regions and underestimate the precision in other regimes with Fisher information tools' help. Notably, a specific choice of the initial Gaussian state's variance in position space will improve the measuring accuracy when we take the kinetic energy term into account. We also study the realistic measurement of the Rabi frequency for cases with and without the kinetic energy. [ABSTRACT FROM AUTHOR]

Direct reduction of bicarbonate, a typical product of CO2 captured in alkaline solution, into value-added organics is one promising way to achieve a simplified and green CO2 capture and utilization process. In this work, a new strategy of bicarbonate reduction coupled with methanol oxidation into a dual formation of formate under mild hydrothermal conditions is reported. A 68% formate production efficiency based on the reductant methanol and nearly 100% selectivity of formate were obtained via a Pd0.5Cu0.5/C catalyst at 180 °C. An operando hydrothermal ATR-FTIR study proved that the bicarbonate was reduced by the in situ generated hydrogen from methanol, which was stepwise oxidized to formaldehyde and formic acid. Notably, DFT calculations and a qNMR study of the 13C and 2H (D) isotopic labelling revealed that H2O molecules not only supplied the hydrogen for bicarbonate reduction but also acted as an indispensable promoter to enhance the catalytic performance of Pd0.5Cu0.5/C for methanol activation. [ABSTRACT FROM AUTHOR]

We study the role of in-situ stresses in fluid flow and mass transport through a two-dimensional fractured rock. The fracture network is based on a real outcrop with a connectivity state around the percolation threshold. We simulate stress-dependent fracture propagation and deformation using a geomechanics model based on the hybrid finite-discrete element method. The hydrodynamic transport through the deformed rock mass is then modeled based on particle tracking simulations. By exploring various scenarios of different stress ratios and orientations, we systematically analyzed how the superimposed multiple geomechanical processes (i.e., compression-induced closure, shear-induced dilation, and stress-induced propagation) control the aperture patterns, flow fields, and transport behaviors of the fracture network. Our results show that an increased stress ratio tends to promote fracture shear dilation and thus enhance flow channelization, resulting in an anomalously early arrival of solute transport. Furthermore, the increased differential stress attempts to drive the growth of wing cracks that bridge pre-existing fractures and form new flow pathways. We observe a qualitative transformation of the flow structure from a disconnected to a connected regime accompanied by a significant alteration of its overall transport properties. This phenomenon is attributed to the superimposed effect of stress-driven crack propagation and shear-induced fracture dilation. By quantitative parameter analyses of global flow and transport properties, we further found that the breakthrough time median of particles is well correlated with the equivalent permeability of the fractured rock when the effect of new cracks is removed. However, this correlation is greatly reduced when fracture propagation is considered; instead, the breakthrough time shows a good correlation with mean tortuosity. Our findings have important implications for the strategy design of geothermal production and waste disposal in critically connected fractured geological media under various stress conditions. • Geomechanical control on fracture aperture, fluid flow and transport in critically connected fracture networks is studied. • Stress-driven crack growth may lead to fundamental changes in transport structure. • New crack formation bridges unconnected fracture clusters to promote stronger anomalous transport. [ABSTRACT FROM AUTHOR]

This article explores a recent tendency in the official Chinese discourse on nationalism—the government more actively employs Chinese achievements in science and technology to boost national pride and regime legitimacy. This "techno-turn" focuses on China's construction of megaprojects, its active role in international techno-economic business, and its development of cutting-edge scientific research and technologies. This transition in the official discourse on nationalism contains several rationales along material, policy, and ideological dimensions, and uses sophisticated propaganda tactics. It also faces constraints and challenges—some derived from conflicts with reality, and others derived from internal logical imbalances. The turn marks a new stage in the development of contemporary Chinese nationalism, in which official nationalism absorbs elements from popular nationalism. This ideological transition may influence both Chinese domestic and international politics—it may lead to China's more confident engagement in international affairs, but may also generate uncertainties in relations between China and the West. [ABSTRACT FROM AUTHOR]

Summary: In medical studies, it is often observed that a portion of subjects will never experience the event of interest and thus can be treated as cured or long‐term survivors. Many populations of early‐stage cancer patients contain both uncured and cured individuals that should be modeled using cure models. In prognostic studies, the cure status (uncure or cure) is an issue of interest for medical practitioners, and the disease status (death or alive) of an individual is not a fixed characteristic and it varies along the time. These statuses are usually predicted by a prognostic risk score. The time‐dependent receiver operating characteristic (ROC) curve is a powerful tool to evaluate these predicting performances dynamically. In the context with a cure fraction, quantifying and estimating the predictive performances of the risk score is a challenge since the disease status and cure status are both unknown among individuals who are censored. In this paper, to assess the predictive accuracy for the survival outcome with a cure fraction, we propose a time‐dependent ROC curve semi‐parametric estimator based on the sieve maximum likelihood (ML) estimation under the mixture cure model. We also apply a Bernstein‐based smoothing method in the estimation procedure, and this estimator can lead to substantial gain in efficiency. In addition, we derive the time‐dependent area under the ROC curve (AUC) to summarize the discriminatory capacity of the risk score globally. Finally, we evaluate the finite sample performance of the proposed methods by extensive simulations and illustrate the estimation using two real data sets, one from a melanoma study and the other from stomach cancer. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of tumor mortality worldwide. However, the mechanisms underlying NSCLC tumorigenesis are incompletely understood. TAGLN, also named SM22, as a member of the calponin family, is highly expressed in many types of tumors. Nevertheless, its effects on NSCLC progression remain unclear. In this study, we found that TAGLN was over-expressed in tumor tissues of NSCLC patients and cell lines. Additionally, NSCLC patients with high expression showed worse overall survival rate. Then, gene silencing results indicated that TAGLN knockdown markedly inhibited proliferation and induced apoptosis in NSCLC cells, while rescue study exhibited opposite results. Moreover, suppressing TAGLN significantly reduced migration and invasion of NSCLC cells, and its over-expression promoted the migratory and invasive activities of NSCLC cells. The in vivo studies confirmed the oncogenic roles of TAGLN in NSCLC, along with clearly elevated metastasis. Notably, these effects were abrogated in mice with TAGLN deletion. Finally, we found that TAGLN knockdown could improve the sensitivity of NSCLC cells to sorafenib (SFB) and 5-FU treatment, further suppressing the proliferation, migration and invasion of NSCLC cells. Consistently, TAGLN deletion attenuated tumor xenografts growth and metastasis of NSCLC in mouse models by enhancing the anti-cancer effects of SFB and 5-FU. Altogether, these findings demonstrated that TAGLN functioned as an oncogene as well as a chemotherapeutic regulator during NSCLC development, which suggested a potential therapeutic strategy for NSCLC treatment mainly through repressing TAGLN expression. • TAGLN is up-regulated in NSCLC and contributes to cell proliferation. • TAGLN promotes migration and invasion abilities of NSCLC cells through inducing EMT. • TAGLN knockdown improves the chemosensitivity of NSCLC cells to sorafenib and 5-FU. • TAGLN promotes tumor growth and metastasis in mice. [ABSTRACT FROM AUTHOR]

Clustered and multivariate survival times, such as times to recurrent events, commonly arise in biomedical and health research, and marginal survival models are often used to model such data. When a large number of predictors are available, variable selection is always an important issue when modeling such data with a survival model. We consider a Cox's proportional hazards model for a marginal survival model. Under the sparsity assumption, we propose a penalized generalized estimating equation approach to select important variables and to estimate regression coefficients simultaneously in the marginal model. The proposed method explicitly models the correlation structure within clusters or correlated variables by using a prespecified working correlation matrix. The asymptotic properties of the estimators from the penalized generalized estimating equations are established and the number of candidate covariates is allowed to increase in the same order as the number of clusters does. We evaluate the performance of the proposed method through a simulation study and analyze two real datasets for the application. [ABSTRACT FROM AUTHOR]

Medical advances including the neoadjuvant anti-PD-1 immunotherapy play a role in promoting clinical outcomes such as improved overall and progression-free survival probabilities. This paper considers the regression analysis of current status data with a cured subgroup in the population using a semiparametric non-mixture cure model. We propose a sieve maximum likelihood estimation for the model with the Bernstein polynomials. Moreover, an expectation–maximization (EM) algorithm is developed under the non-mixture cure model to calculate the estimators for both parametric and non-parametric components. Under some mild conditions, the asymptotic properties of the estimators are established, including the strong consistency, the convergence rate and the asymptotic normality. Simulation studies are conducted to investigate the finite sample performance of the proposed estimators. A real dataset from the tumorigenicity experiment is analysed for illustration. [ABSTRACT FROM AUTHOR]

• A novel method of bicarbonate reduction into a C2 product of acetate is proposed. • Water acts as both facile hydrogen source and environmental-friendly solvent. • in situ formed Raney-Ni/Fe 3 O 4 catalyzes the formation of acetate. • Achieved C C bond formation and C2 product generation on a non-noble metal catalyst. Conversion of CO 2 into value-added chemicals is always of great interest. Previous research mainly focuses on the CO 2 conversion into C1 chemicals such as formic acid. In this research, a new approach of reducing bicarbonate (CO 2 source) into a C2 compound of acetate with water as the hydrogen source and Fe as re-generable reductant on a Raney-Ni (R-Ni) catalyst was proposed by mimicking the natural abiotic organic synthesis found in the deep-sea hydrothermal vent. During the reaction, the in situ formed Fe 3 O 4 together with the R-Ni generated a R-Ni/Fe 3 O 4 bifunctional catalyst, in which the in situ formed Fe 3 O 4 probably promote a high adsorption enthalpy of C1 intermediates on the Ni catalyst, leading to an optimum acetate yield of 4.1%. Mechanistic study revealed that the catalytic mechanism of the R-Ni/Fe 3 O 4 was probably attributed to i) enhancement of in situ hydrogen activation and formate synthesis over the Fe 3 O 4 site; ii) CO formation and activation over the Raney-Ni site; iii) formation and adsorption of methylene from CO on the R-Ni surface; and iv) acetate formation from the combination of formate and methylene over R-Ni site. This research developed a new way to reduce CO 2 into C2 products with water as the hydrogen source, which provides new insights into the CO 2 conversion to products with C ≥ 2. [ABSTRACT FROM AUTHOR]

Monitoring of any manufacturing, production, or industrial process can be controlled and improved by removing these special cause of variations using control charts. Shewhart‐type control charts are effective to control a large amount of special variations, whereas, cumulative sum (CUSUM) and exponentially weighted moving average (EWMA) charts detect small and moderate variations efficiently in the process parameters. Monitoring of location parameter can be done with mean control charts under the assumption that the parameters are known or correctly estimated from in‐control samples and data are free from outliers (but in practice data occasionally have outliers). In this study, we have proposed generalized mixed EWMA‐CUSUM median control charts structures for known and unknown parameters based on auxiliary variables for detecting shifts in process location parameter. The proposed charts are compared with the corresponding charts for the mean, based on contaminated and uncontaminated data. Different performance measures are used to evaluate the performance of proposed control charts and revealed through results that the median‐based charts are more sensitive to detect a shift in process location parameter in the presence of outliers. An illustrative example using real data is also shown for practical consideration. [ABSTRACT FROM AUTHOR]

In reliability or survival analysis, the hazard function plays a significant part for it can display the instantaneous failure rate at any time point. In practice, the abrupt change in hazard function at an unknown time point may occur after a maintenance activity or major operation. Under these circumstances, identifying the change point and estimating the size of the change are meaningful. In this paper, we assume that the hazard function is piecewise constant with a single jump at an unknown time. We propose the single change-point model for interval-censored survival data with a cure fraction. Estimation methods for the proposed model are investigated, and large-sample properties of the estimators are established. Simulation studies are carried out to evaluate the performance of the estimating method. The liver cancer data and breast cancer data are analyzed as the applications. [ABSTRACT FROM AUTHOR]

We investigated the effect of in situ stresses on fluid flow in a natural fracture network. The fracture network model is based on an actual critically connected (i.e., close to the percolation threshold) fracture pattern mapped from a field outcrop. We derive stress-dependent fracture aperture fields using a hybrid finite-discrete element method. We analyze the changes of aperture distribution and fluid flow field with variations of in situ stress orientation and magnitude. Our simulations show that an isotropic stress loading tends to reduce fracture apertures and suppress fluid flow, resulting in a decrease of equivalent permeability of the fractured rock. Anisotropic stresses may cause a significant amount of sliding of fracture walls accompanied with shear-induced dilation along some preferentially oriented fractures, resulting in enhanced flow heterogeneity and channelization. When the differential stress is further elevated, fracture propagation becomes prevailing and creates some new flow paths via linking preexisting natural fractures, which attempts to increase the bulk permeability but attenuates the flow channelization. Comparing to the shear-induced dilation effect, it appears that the propagation of new cracks leads to a more prominent permeability enhancement for the natural fracture system. The results have particularly important implications for predicting the hydraulic responses of fractured rocks to in situ stress fields and may provide useful guidance for the strategy design of geofluid production from naturally fractured reservoirs. [ABSTRACT FROM AUTHOR]

The receiver operating characteristic (ROC) curve is a graphical representation of the relationship between false positive and true positive rates. It is a widely used statistical tool for describing the accuracy of a diagnostic test. In this paper we adopt Bernstein polynomials to construct the ROC curve estimator. The consistency rate of this estimator is studied. We also obtain explicit expressions for the asymptotic bias and variance and show the improvement of the asymptotic mean squared error compared to that of the classical empirical ROC estimator. Furthermore, the weak convergence of the Bernstein ROC process is established. Simulation studies are conducted to compare our proposed estimator with other popular nonparametric ROC estimators. Finally, the proposed method is illustrated by application to a real data set. [ABSTRACT FROM AUTHOR]

• A model of incipient karst formation in realistic fracture networks is proposed. • Two distinctive dissolution behaviors are related to two types of flow organization. • If flow is normal to persistent fractures, the positive feedback loop is periodically interrupted. • Relation between karst models based on dissolution and generic growth kinetics is discussed. Karst features in limestone aquifers often exhibit highly heterogeneous patterns, which are strongly governed by structural complexities such as the spatial distribution and organization of fractures in natural carbonate rocks. However, until now, little is known about the impact of structural complexity on karstification processes. In this paper, we use numerical models to investigate how structural heterogeneity affects the generation of incipient karst in natural fractured systems. We develop a numerical model which couples the processes of fluid flow, mass transport and dissolution kinetics that govern the growth of fracture aperture, based on discrete fracture networks. We apply the model to simulate conduit evolution in a natural joint network that displays a distinctive topological pattern. A wide range of hydraulic gradient and initial fracture aperture is considered. Our results show that the network topology may generate a significant impact on dissolution pattern depending on how flow is organized within the discrete network. If a channelized structure occurs in the flow network, the dissolution pattern depends highly on the initial hydrogeological settings, while if the flow network consists of branched segments, a similar dissolution pattern emerges for a broad range of initial hydrogeological settings. When the flow direction is normal to the persisting fracture orientation, intermittent interruptions to the positive feedback process between flow and dissolution occur. Therefore, the breakthrough is delayed. We discuss the link between our results of dissolution modeling in fracture networks to previous modelling efforts in the context of single rough fractures and fracture network formed by orthogonal fracture sets. [ABSTRACT FROM AUTHOR]

Efficient development of hot dry rock (HDR) relies on a thorough assessment of the extraction potential. Stimulated reservoir volumes (SRV) and hydraulic fractures are the primary sites for water circulation and heat exchange in the heat mining process, and thus are crucial to HDR development. The objective of this study is to investigate the heat extraction performance of HDR reservoir under the interplay between the heterogeneous fracture and SRV, which can enhance the thorough understanding of the heat extraction process of stochastic HDR reservoirs and contribute to optimizing the design of the HDR development. A series of 3D thermal-hydraulic-mechanical coupling models with different permeability distributions were established innovatively. Results indicated that the homogeneous reservoir with a 35-year operation time yields an outlet temperature ranging from 161 to 131.8 °C, a thermal breakthrough time of 18 years, a production thermal power between 14.5 and 10.5 MW, and a maximum heat extraction ratio of 32%. Spatial heterogeneity in the fracture permeability significantly impacted the reservoir productivity by creating preferential flow channels. Introducing heterogeneity with a variance of 1 and correlation length of 60 m resulted in a reduction of 4.4 °C in the outlet temperature, 1 year in thermal breakthrough time, 0.6 MW in production thermal power, and 1% in heat extraction ratio compared to homogeneous reservoirs. Moreover, the heterogeneous permeability in SRV further decreased heat mining capability, with a reduction of approximately 14.8 °C, 10 years, 1.9 MW, and 5.17% observed when incorporating SRV heterogeneity (variance of 2 and correlation length of 120 m) into the reservoir already subjected to heterogeneous fracture. This study also provided valuable insights into how stress conditions affect the performance of a reservoir with the heterogeneous fracture and SRV. The results pointed out that applying in situ stress lowered reservoir attenuation rate and allowed for greater heat extraction compared to the reservoir without in situ stress. This can be attributed to the less dispersed fracture permeability occurring under in-situ stress, which caused by the reduced sensitivity of permeability to stress under high-stress conditions. Results also demonstrated that the thermal breakthrough time is the most sensitive performance metric to the variations of the fracture and SRV permeability, followed by the output thermal power, heat extraction ratio, and finally the produced temperature. • Combined effects of heterogeneous fracture and SRV permeabilities on geothermal production from HDR are studied using a coupled THM model. • Increase in permeability heterogeneity results in decreased heat extraction efficiency. • Thermal breakthrough time is the most sensitive heat extraction efficiency indicator to permeability heterogeneity. [ABSTRACT FROM AUTHOR]

Huoluo Xiaoling Pellet (HXP), a Chinese patent medicine, is commonly administered for the treatment of treat ischemic strokes. MCPIP1, an inducible suppressor of the inflammatory response, is a regulator of microglial M2 polarization. This study aimed to explore whether HXP can promote microglial M2 polarization by upregulating MCPIP1 expression, consequently mitigating cerebral ischemic injury. Our study involved 85 Sprague-Dawley rats (weighing 250–280 g). We established middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation-reoxygenation (OGD/R) models with MCPIP1 knockdown to assess the effects of HXP on ischemic strokes. Our findings show that HXP reduced brain water content, improved neurological function, and inhibited the expression of inflammatory factors in the brain tissues of MCAO rats. The neuroprotective effects of HXP on cerebral ischemic injuries were compromised by MCPIP1 knockdown. Immunofluorescence results indicated that the expression of microglia marker Iba1 and M2 phenotypic marker CD206 was upregulated in MCAO rats and OGD/R-treated microglia. Administration of HXP significantly reduced Iba1 expression and facilitated CD206 expression, an effect that was counteracted by sh-MCPIP1 transfection. Western blotting revealed that HXP treatment augmented the expression of MCPIP1, microglial M2 marker proteins (CD206 and Arg1), and PPARγ, while reducing the expression of microglial M1 marker proteins (CD16 and iNOS) in MCAO rats and OGD/R-induced microglia. MCPIP1 knockdown suppressed HXP-mediated upregulation of MCPIP1, CD206, Arg1, and PPARγ, as well as the downregulation of CD16 and iNOS. Our findings suggest that HXP primarily ameliorates ischemic stroke through the upregulation of MCPIP1, which in turn induces microglial M2 polarization. [Display omitted] • HXP upregulated MCPIP1 expression in MCAO rats and OGD/R microglia. • HXP promoted microglia M2 polarization via the upregulation of MCPIP1 expression. • HXP alleviated ischemia stroke via MCPIP1-induced microglia M2 polarization. [ABSTRACT FROM AUTHOR]

Abstract The ways in which urban rail transit influences land development have been extensively studied for cities in the United States and Europe; studies from less-developed countries are limited. However, the influences of rail transit on land development in developing countries such as China have drawn much scholarly attention in recent years, in part due to the unprecedented speed and scale of its urbanization and development of rail systems. The main research questions of the present study are whether rail transit attracts new developments or redevelopment to areas surrounding stations and whether the city-shaping ability of rail transit differs between central areas and suburbs. Our study focused on Shenzhen, one of the most quickly urbanizing areas in China. We utilized land parcel data in Shenzhen collected in two different years and applied multiple linear regressions with interactive terms to compare the effect of rail transit stations on land development by region (i.e., central areas vs. suburbs). The evidence supported our hypothesis that the densifying of land development brought on by rail transit is more prominent in already developed central areas than in low-density suburbs. Our research findings help illuminate the interactive relationships between transportation and land development in China; this study also contributes to the broader discussion of sustainable urbanization. Highlights • The main research questions are whether rail transit attracts new developments or redevelopment to areas surrounding stations and whether the city-shaping ability of rail transit differs between central areas and suburbs. • We utilized land parcel data in Shenzhen collected in two different years and applied multiple linear regressions with interactive terms to compare the effect of rail transit stations on land development by region (i.e., central areas vs. suburbs). • The evidence supported our hypothesis that the densifying of land development brought on by rail transit is more prominent in already developed central areas than in low-density suburbs. [ABSTRACT FROM AUTHOR]

Nitrate and nitrite reduction are of paramount importance for nitrogen assimilation and anaerobic metabolism, and understanding the specific roles of each participating reductase is necessary to describe the biochemical balance that dictates cellular responses to their environments. The soluble, cytoplasmic siroheme NADH-nitrite reductase (Nir) in Escherichia coli is necessary for nitrate/nitrite assimilation but has also been reported to either "detoxify" nitrite, or to carry out fermentative ammonification in support of anaerobic catabolism. Theoretically, nitrite detoxification would be important for anaerobic growth on nitrate, during which excess nitrite would be reduced to ammonium. Fermentative ammonification by Nir would be important for maximization of non-respiratory ATP production during anaerobic growth in the presence of nitrite. Experiments reported here were designed to test the potential role of Nir in fermentative ammonification directly by growing E. coli along with mutant strains lacking Nir or the respiratory nitrite reductase (Nrf) under anaerobic conditions in defined media while monitoring nitrogen utilization and fermentation metabolites. To focus on the role of Nir in fermentative ammonification, pH control was used in most experiments to eliminate nitrite toxicity due to nitric acid formation. Our results demonstrate that Nir confers a significant benefit during fermentative growth that reflects fermentative ammonification rather than detoxification. We conclude that fermentative ammonification by Nir allows for the energetically favorable fermentation of glucose to formate and acetate. These results and conclusions are discussed in light of the roles of Nir in other bacteria and in plants. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New N -phenylpyrazole-containing 8-hydroxyquinaldine derivatives were prepared. • An efficient way for one pot synthesis of the target compounds was developed. • Compounds 8g and 9f exhibited potent pesticidal activities. • The structure-activity relationships were also discussed. Abstract In continuation of our research aimed at discovery and development of new pesticidal agents, a series of new 8-hydroxyquinaldine derivatives containing a N –phenylpyrazole moiety were prepared and their structures were characterized by 1H NMR, IR, ESI-MS and mp. Meanwhile, an efficient way of using iodine-mediated oxidative cyclization for one pot synthesis of these 8-hydroxyquinaldine derivatives containing a N –phenylpyrazole moiety was developed. The bioassay showed that compounds 8g and 9f exhibited potent pesticidal activities against both Mythimna separata Walker and Plutella xylostella Linnaeus. The structure–activity relationships were also discussed. [ABSTRACT FROM AUTHOR]

Receiver operating characteristic (ROC) curve has been widely used in medical diagnosis. Various methods are proposed to estimate ROC curve parameters under the binormal model. In this paper, we propose a Bayesian estimation method from the continuously distributed data which is constituted by the truth-state-runs in the rank-ordered data. By using an ordinal category data likelihood and following the Metropolis-Hastings (M-H) procedure, we compute the posterior distribution of the binormal parameters, as well as the group boundaries parameters. Simulation studies and real data analysis are conducted to evaluate our Bayesian estimation method. [ABSTRACT FROM AUTHOR]

Image segmentation plays an important role in image processing before image recognition or compression. Many segmentation solutions follow the information theoretic criteria and often have excellent results; however, they are not robust to reduce the noise effect in contaminated image data. To guarantee the optimal segmentation with possible noise, a robust Bayesian information criterion is proposed to segment a grayscale image and it is less sensitive to noise. The asymptotic properties are also studied. Monte Carlo numerical experiments along with a brain magnetic resonance image are conducted to evaluate the performance of the new method. [ABSTRACT FROM AUTHOR]

Highlights • A new method for characterizing horizontal transmissivity anisotropy using cross-hole slug tests is proposed. • The method is validated by a numerical example and against Papadopulos’ method based on cross-hole pumping tests. • Effects of heterogeneity, measurement scale and medium connectivity on the tensor analysis were discussed. Abstract Traditional methods for characterizing horizontally anisotropic aquifers are all based on pumping tests. In this paper, we present a new method for the identification of horizontal anisotropy using cross-hole slug tests, which is much more easily accessible comparing to pumping tests. Through scaler transform, an anisotropic medium was converted into an equivalent isotropic medium. When applying the analytical solutions derived for isotropic media to interpret cross-hole slug tests performed in anisotropic media, the estimated transmissivity is the geometrical mean of the anisotropic transmissivity tensor, regardless of sampling direction. However, the apparent storativity calculated from different observation wells, is equal to the true storativity scaled by a factor defined by the formation anisotropy. Thus, anisotropy can be resolved through apparent storativity that bears directional information. The proposed method was first validated by a numerical experiment and then applied to field data. It was found that the tensor results obtained by this new method with cross-hole slug tests are consistent with that obtained by applying the classical Papadopulos’ method with cross-hole pumping tests conducted in the same wells. When applied to heterogeneous media, tensor results produced by the new method may be subject to considerable errors. This is because the results are strongly sensitive to the connectivity between measurement boreholes and the formation medium. To reduce the error level, responses from a large number of observation wells located in various directions around the source well are needed. In addition to the adopted KGS solution for confined aquifers, the proposed methodology can be applied to incorporate other analytical methods for a variety of aquifer types, as long as the characteristic relationship between the measure scale and the aquifer storativity can be established. [ABSTRACT FROM AUTHOR]

Background and objective : Most of available software packages for mixture cure models to analyze survival data with a cured fraction assume independent survival times, and they are not suitable for correlated survival times, such as clustered survival data. The objective of this paper is to present a software package to fit a marginal mixture cure model to clustered survival data with a cured fraction. Methods : We developed an R package geecure that fits the marginal proportional hazards mixture cure (PHMC) models to clustered right-censored survival data with a cured fraction. The dependence among the cure statuses and among the survival times of uncured patients within a cluster are modeled by working correlation matrices through the generalized estimating equations, and the Expectation-Solution algorithm is used to estimate the parameters. The variances of the estimated regression parameters are estimated by either a sandwich method or a bootstrap method. Results : The package geecure can fit the marginal PHMC model where the cumulative baseline hazard function is either a two-parameter Weibull distribution or specified nonparametrically. Fitting the parametric PHMC model with the Weibull baseline hazard function on average takes less time than fitting the semiparametric PHMC model does. Two variance estimation methods are comparable in the simulation study. The sandwich method takes much less time than the bootstrap method in variance estimation. Conclusions : The package geecure provides an easy access to the marginal PHMC models for clustered survival data with a cured fraction in routine survival analysis. It is easy to use and will make the wide applications of the marginal PHMC models possible. [ABSTRACT FROM AUTHOR]

Yes-associated protein (YAP) serves an essential role in tumorigenesis. However, the potential role and the molecular mechanism underlying the effect of YAP on hepatocellular carcinoma (HCC) cells have not been elucidated. In the current study, it was revealed that YAP expression was increased significantly in HCC cancer tissues and its overexpression was associated with tumor differentiation. The silencing of YAP by small interferring RNA led to the inhibition of HCC cell growth, which was associated with the promotion of apoptosis. The silencing of YAP also decreased the invasive potential of HCC cells and the activity of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. Furthermore, silencing of YAP increased the chemosensitivity of HCC cells to cisplatin (CDDP) through inactivation of the PI3K/AKT signaling pathway. In vivo studies using PDTX model suggested a promotive role for YAP in the growth of HCC and knockdown of YAP increased the anti-tumor activity of CDDP. Taken together, these results revealed that YAP is overexpressed in HCC, and promotes proliferation, invasion and drug resistance of HCC cells. Inhibition of YAP, alone or in combination with traditional chemotherapy, may effectively combat HCC. [ABSTRACT FROM AUTHOR]

Background and aims: The nitrogen isotope composition (δ15N) of plants in arid and semiarid grasslands is affected by environmental factors, especially water availability. Nevertheless, it is unclear whether the response of δ15N to water availability differs between C3 and C4 photosynthetic pathways.Methods: We investigated plant δ15N of coexisting C3 and C4 species as a function of aridity along a 3200 km aridity gradient across the arid and semi-arid grasslands of northern China.Results: Aridity was positively correlated with plant δ15N values in both C3 and C4 plants and also in the entire plant community, whereas soil bulk δ15N values increased first and then decreased along the aridity gradient. The N uptake by C4 plants appeared to be more affected by competition pressure of neighboring plants and soil microbes than for C3 plants along the transect.Conclusions: The decoupled relationship between plant and soil δ15N values indicated that variations in vegetation and soil δ15N values were driven by differential biogeochemical processes, while different soil N sources were used for plant growth along the climatic gradient. The advantage of C3 plants in the use of N may counteract the competitive advantage that C4 plants have over C3 plants due to their higher water use efficiency under drier conditions. These findings can help understand why C4 plants do not completely replace C3 plants in drier environments despite their higher water use efficiency. [ABSTRACT FROM AUTHOR]